Dry eye composition and method for preparing the composition

ABSTRACT

An ophthalmic composition of water soluble ingredients provides additional moisture to the eye by promoting moisture absorption from the air and providing long lasting relief. The composition can include two groups of ingredients, one a liquid and the other a solid. Together, the ingredients form a substance that ranges from a liquid to a gel. Benefits of such composition include longer lasting symptom relief with less applications and increased moisture production.

CROSS-REFERENCE TO RELATED APPLICATION

This non-provisional patent application claims priority under 35 U.S.C.§119(e) to U.S. Provisional Patent Application, Ser. No. 62/056,373,filed Sep. 26, 2014, the disclosure of which is incorporated byreference.

FIELD

The invention relates in general to ophthalmic compositions, and inparticular, to dry eye and dry skin compositions and methods forpreparing the compositions.

BACKGROUND

Dry eye is one of the most common ophthalmologic problems experienced byindividuals. Dry eye occurs when an individual fails to produce asufficient quantity or quality of tears to lubricate and nourish theeye, such as due to aging, long-term contact lens wear, environmentaleffects, or as a side effect of certain medications, includingantihistamines and antidepressants. Further, a failure to produce tearsor to produce an adequate quantity or quality of tears can occur basedon an inability of the eyelids to close completely over the eye, eyeliddisease, and a deficiency of tear-producing glands. Individuals with dryeye often experience symptoms of dryness, scratchiness, red eyes, and aburning sensation that is irritating and uncomfortable.

Depending on the cause, dry eye can be considered a chronic and oftenprogressive condition that can be managed via eye drops, topicalpreparations, change in environment, change in nutrition, or medication,as well as other means. In mild cases, dry eye is generally managedusing eye drops that can be obtained over the counter or via aprescription from a doctor to supplement tear production. However, someeye drops are more effective than others for treating dry eye and mostprovide only a short period of relief, thus, requiring many applicationsthroughout the day. Topical preparations are also commonly used toprovide dry eye relief. However, conventional topical preparationsgenerally only include small amounts of moisturizers, and thus, onlyprovide short periods of relief. Like eye drops, gels also only providea short period of relief, while ointments, which are applied to the eye,provide a longer relief period. Yet, ointments can cause blurred visionand can be difficult to apply.

Accordingly, there remains a need for a dry eye composition thatprovides long lasting ocular comfort that is easy to apply and providesalleviations of dry eye symptoms. Preferably, the composition does notblur vision.

SUMMARY

Currently, eye drops and ointments are frequently recommended fortreating dry eye. However, conventional products include water-solubleingredients in small amounts and offer only short periods of relief withmultiple applications to provide longer periods of comfort. Acomposition of water soluble ingredients in a much higher concentrationprovides additional moisture to the eye by promoting moisture absorptionfrom the air and provides long lasting relief. The composition caninclude two groups of ingredients, one a liquid and the other a solid.Together, the ingredients form a substance that ranges from a cream toan ointment to a semi-solid. Benefits of such composition include longerlasting symptom relief with less applications and increased moistureproduction.

Still other embodiments will become readily apparent to those skilled inthe art from the following detailed description, wherein are describedembodiments by way of illustrating the best mode contemplated. As willbe realized, other and different embodiments are possible and theirseveral details are capable of modifications in various obviousrespects, all without departing from the spirit and the scope.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not as restrictive.

DETAILED DESCRIPTION

Individuals with dry eye can experience a multitude of symptoms,including eye dryness, scratchiness, red eyes, a burning sensation,blurred vision, sensitivity to light and eye fatigue. Relief of dry eyesymptoms can occur, inter alia, via eye drops or other lubricants,medication, and a change of environmental setting. Eye drops and gelsare often recommended due to their ease of application, but only providea short period of relief. In contrast, ointments provide longer lastingrelief, but are difficult to apply. Further, currently available gelsand ointments include water-soluble ingredients in small amounts that donot provide lasting relief.

A composition of water soluble ingredients promotes absorption ofmoisture from the air to increase moisture on the surface of the eye.The water soluble ingredients include a liquid and a solid that, whencombined, form a substance that varies between a cream, ointment, orsemi-solid. The first group includes a solid polyethylene glycol (PEG),while the second group includes a liquid, such as a modified glycerin,commonly known as Glycereth. Solid PEGs can have a molecular weight from1400 to 9000.

The glycerin is modified by adding PEG adducts on one or more of thehydroxyl groups of the glycerin. Each modified form of glycerin is thenidentified by a number from one to 30, which represents a total numberof ethoxy groups attached to the three hydroxyl groups of the glycerin.The total number of ethoxy groups is provided as an average. Forexample, for Glycereth 26, each modified glycerin has an average of 26ethoxy groups. As more ethoxy groups are added, the vapor pressure isreduced.

One exemplary ophthalmic composition is a creamy gel for dry eye reliefthat is prepared with the components and amount listed in the tablebelow:

TABLE 1 Minimum Maximum Preferred Component Amount Amount Amount PEG3350 10.0% 80.0% 60.0% Glycereth 26 10.0% 80.0% 15.0% H₂O 10.0% 80.0%24.1% NaC1 0.0% 0.9% 0.9%

The values provided in the table above specify an amount by weight basedon a total weight of the composition. Although PEG 3350 is a listedcomponent, all grades of PEG from PEG 1400 to PEG 9000 are possible inlieu of PEG 3350. However, PEG 3350 has a medium molecular weight, andis readily available and easiest to procure. When a form of PEG is usedwith a higher molecular weight, a lesser amount of the PEG is needed,while a larger amount of water is required to obtain a desiredconsistency. Glycereth 26 has a higher molecular weight than many otherforms of Glycereth and a slower evaporation weight, which results inlonger lasting relief of dry eye symptoms. Glycereth 26 can be obtained,for example, from Lipo Chemicals Inc., Paterson, N.J., as Liponic EG-1.However, in a further embodiment, different forms of Glycereth can beused, including Glycereth 1 through 30, in the amounts provided in thetable above. Water is added to the combination of PEG and Glycereth togenerate a composition that is of a proper viscosity to be applied to apatient's eye. The proper viscosity can be anything softer than a solid,such that the composition can be applied to a patient's eye. The sodiumchloride can be added to the PEG-Glycereth combination to imitate realtears, which generally include 0.9% sodium chloride. The sodium chloridecan equalize the ophthalmic composition and prevent stinging uponapplication of the composition. However, in a further embodiment, thesodium chloride can be removed from the composition described above inTable 1. In yet a further embodiment, the Glycereth can be replaced withany liquid polyethylene glycol, in the same amounts listed in the tableabove for Glycereth.

To prepare the composition, amounts of the components listed in theabove-identified table are determined. Next, all the components arecombined at the same time in the determined amounts and heated to about130 to 150 degrees until the PEG is completely dissolved usingconventional methods well known in the art. Once dissolved, the combinedsolution is stirred while cooling until a white creamy semi-solid, suchas a gel, is formed.

The semi-solid ophthalmic composition described above is self-preservingand can be stored in a plastic tube, bottle, or eye drop dispenser forproviding to a patient in need of dry eye relief. The appearance andform of the ophthalmic composition is a white semi-solid or gel, and thecomposition is intended to be available to patients without aprescription. In a preferred embodiment, the patient applies theophthalmic composition to the eye, specifically, the inferior palperbralconjunctiva, via an eye dropper or a single use applicator. If thepatient wears contact lenses, the contact lenses should be removed priorto application of the ophthalmic composition. A single use applicationcan include the appropriate amount of the ophthalmic composition, whilethe eye dropper can be metered to release one to two drops.

In a further embodiment, the patient can squeeze the ophthalmiccomposition out of the tube or bottle onto his finger or another object,such as a cotton ball or Q-tip. Subsequently, the patient applies theophthalmic composition to his eye, particularly, the inferior palperbralconjunctiva via the finger or other object. The ophthalmic compositionshould be applied to each eye affected by dry eye symptoms, on an asneeded basis. The ophthalmic composition can provide longer relief fromdry eye than currently available eye solutions. Effectiveness of theophthalmic composition can last up to a maximum of 18 hours and one ortwo applications of the ophthalmic composition per day may beappropriate. However, additional applications may be necessary.

Another exemplary composition for dry eye relief is prepared with thecomponents and amounts listed in the table below:

TABLE 2 Minimum Maximum Preferred Component Amount Amount Amount PEG3350 10.0% 59.1% 19.6% Glycereth 26 10.0% 59.1% 30.0% H₂O 30.0% 79.1%50.0% Carboxymethylcellulose 0.1% 3.0% 00.4% Sodium

The values provided in the table above specify an amount by weight basedon a total weight of the composition. Although PEG 3350 is a listedcomponent, all grades of PEG from PEG 1400 to PEG 9000 are possible inlieu of PEG 3350. However, PEG 3350 has a medium molecular weight, andis readily available and easiest to procure. When a form of PEG is usedwith a higher molecular weight, a lesser amount of the PEG is needed,while a larger amount of water is required to obtain a desiredconsistency. Glycereth 26 has a higher molecular weight than many otherforms of Glycereth and a slower evaporation rate, which results inlonger lasting relief of dry eye symptoms. Glycereth 26 can be obtained,for example, from Lipo Chemicals Inc., Paterson, N.J., as Liponic EG-1.However, in a further embodiment, different forms of Glycereth can beused, including Glycereth 1 through 30, in the amounts provided in thetable above. Water is added to the combination of PEG and Glycereth tohelp dissolve the solid PEG and generate a composition that is theproper viscosity to be applied to a patient's eye. The proper viscositycan be anything softer than a solid, such that the composition can beapplied to a patient's eye. The carboxymethylcellulose sodium acts as athickener and can be obtained from The Dow Chemical Company, under thename Walocel CRT. In a further embodiment, the Glycereth can be replacedwith any liquid polyethylene glycol, in the same amounts listed in thetable above for Glycereth.

To prepare the composition, amounts of the components listed in theabove-identified table are determined. Next, all the components are allcombined in the determined amounts and heated to about 180 degrees untilthe PEG and Carboxymethylcellulose Sodium are completely dissolved usingconventional methods well known in the art. Once dissolved, the combinedsolution is allowed to cool, forming semi-solid, such as a colorlesstransparent gel.

The semi-solid ophthalmic composition described above is self-preservingand can be stored in a plastic tube, bottle, or eye drop dispenser forproviding to a patient in need of dry eye relief. The appearance andform of the ophthalmic composition is a transparent gel that can beslightly runny, and the composition is intended to be available topatients without a prescription. In a preferred embodiment, the patientapplies the ophthalmic composition to the eye, specifically, theinferior palperbral conjunctiva, via an eye dropper or a single useapplicator. If the patient wears contact lenses, the contact lensesshould be removed prior to application of the ophthalmic composition. Asingle use application can include the appropriate amount of theophthalmic composition, while the eye dropper can be metered to releaseone to two drops.

In a further embodiment, the patient can squeeze the ophthalmiccomposition out of the tube or bottle onto his finger or another object,such as a cotton ball or Q-tip. Subsequently, the patient applies theophthalmic composition to his eye, particularly, the inferior palperbralconjunctiva via the finger or other object. The ophthalmic compositionshould be applied to each eye affected by dry eye symptoms, on an asneeded basis. The ophthalmic composition can provide longer relief fromdry eye than currently available eye solutions. Effectiveness of theophthalmic composition can last up to a maximum of 18 hours and one ortwo applications of the ophthalmic composition per day may beappropriate. However, additional applications may be necessary.

Another exemplary composition for dry eye relief is prepared with thecomponents and amounts listed in the table below:

TABLE 3 Minimum Maximum Preferred Component Amount Amount Amount PEG3350 10.0% 59.9% 19.6% Glycereth 26 10.0% 59.9% 30.0% NaCl 0.0% 0.9%0.9% Carboxymethylcellulose 0.1% 3.0% 00.4% Sodium H20 30.0 70.0 49.1

The values provided in the table above specify an amount by weight basedon a total weight of the composition. Although PEG 3350 is a listedcomponent, all grades of PEG from PEG 1400 to PEG 9000 are possible inlieu of PEG 3350. However, PEG 3350 has a medium molecular weight, andis readily available and easiest to procure. When a form of PEG is usedwith a higher molecular weight, a lesser amount of the PEG is needed,while a larger amount of water is required to obtain a desiredconsistency. Glycereth 26 has a higher molecular weight than many otherforms of Glycereth and a slower evaporation rate, which results inlonger lasting relief of dry eye symptoms. Glycereth 26 can be obtained,for example, from Lipo Chemicals Inc., Paterson, N.J., as Liponic EG-1.However, in a further embodiment, different forms of Glycereth can beused, including Glycereth 1 through 30, in the amounts provided in thetable above. The sodium chloride can be added to the PEG-Glycerethcombination to imitate real tears, which generally include 0.9% sodiumchloride. The sodium chloride can equalize the ophthalmic compositionand prevent stinging upon application of the composition. Thecarboxymethylcellulose sodium acts as a thickener and can be obtainedfrom The Dow Chemical Company, under the name Walocel CRT. In a furtherembodiment, the Glycereth can be replaced with any liquid polyethyleneglycol, in the same amounts listed in the table above for Glycereth.

To prepare the composition, amounts of the components listed in theabove-identified table are determined. Next, all the components arecombined in the determined amounts and heated to about 180 degrees untilthe PEG and Carboxymethylcellulose Sodium are completely dissolved usingconventional methods well known in the art. Once dissolved, the combinedsolution is allowed to cool, forming a colorless transparent gel.

The semi-solid ophthalmic composition described above is self-preservingand can be stored in a plastic tube, bottle, or eye drop dispenser forproviding to a patient in need of dry eye relief. The appearance andform of the ophthalmic composition is a transparent gel that can beslightly runny. In a preferred embodiment, the patient applies theophthalmic composition to the eye, specifically, the inferior palperbralconjunctiva, via an eye dropper or a single use applicator. If thepatient wears contact lenses, the contact lenses should be removed priorto application of the ophthalmic composition. A single use applicationcan include the appropriate amount of the ophthalmic composition, whilethe eye dropper can be metered to release one to two drops.

In a further embodiment, the patient can squeeze the ophthalmiccomposition out of the tube or bottle onto his finger or another object,such as a cotton ball or Q-tip. Subsequently, the patient applies theophthalmic composition to his eye, particularly, the inferior palperbralconjunctiva via the finger or other object. The ophthalmic compositionshould be applied to each eye affected by dry eye symptoms, on an asneeded basis. The ophthalmic composition can provide relief from dry eyeup to a maximum of 18 hours and one or two applications of theophthalmic composition per day may be appropriate. However, additionalapplications may be necessary.

The minimum and maximum amount ranges listed in Tables 1 through 3 weredetermined through testing of different compositions within thoseranges. Specifically, the minimum and maximum amounts are based on astate of the associated compositions. For instance, in amounts outsideof the identified minimum and maximum ranges, the composition may becomesolid or liquid and thus, inappropriate for proper application to theeye.

Further, ophthalmic compositions as outlined in the preferred amounts ineach of the Tables 1 through 3, were tested on individuals. Thecomposition in Table 2, in the preferred amounts, was given to 38individuals. The test conditions were based on standard clinicaltechniques and no harm was caused to any of the individuals' eyes. Mostof the individuals reported substantial improvement in dry eye symptoms,with only two reporting no improvement. With regards to duration of thedry eye symptom relief, only one of the 38 individuals needed to applythe ophthalmic composition of Table 2 more than twice per day. Whereas,most conventional eye drops require application every one to two hoursto ensure that dry eye symptoms are relieved. Meanwhile, the ophthalmiccomposition, described above in Table 1 was provided, in the preferredamounts, to around five individuals. The test conditions were based onstandard clinical techniques and no harm was caused to any of theindividuals' eyes. Over all, the individuals experienced an improvementin dry eye symptoms, including a duration of relief, but alsoexperienced a mild burning sensation that lasted no longer than tenseconds after application of the ophthalmic composition. Additionally,the ophthalmic composition of Table 3, in the preferred amounts, wastested on around five individuals. The individuals experienced relief ofdry eye symptoms, including a duration of the relief. However, the saltwas difficult to get evenly distributed within the composition.

The dry eye solutions can be slightly modified to prepare a cream or gelfor alleviating dry skin, including providing itch relief. One exemplarycomposition for relief of dry skin is prepared with the components andamount listed in the table below:

TABLE 4 Minimum Maximum Preferred Component Amount Amount Amount PEG3350 5% 95% 12.0% Glycereth 26 5% 95% 88.0%

The composition formed from the components in the table above include ahigher percentage of active ingredients than conventional skincompositions. Additionally, since the above-identified skin compositiondoes not include water, the composition will not dry out as conventionalskin compositions tend to do. Most conventional skin moisturizers areoil-based and prevent drying by hindering the evaporation of moisturealready present. This composition, by comparison, acts by absorbingmoisture from the air.

Although PEG 3350 is a listed component, all grades of PEG from PEG 1400to PEG 9000 are possible in lieu of PEG 3350. However, PEG 3350 has amedium molecular weight, and is readily available and easiest toprocure. When a form of PEG is used with a higher molecular weight, alesser amount of the PEG is needed, while a larger amount of water isrequired to obtain a desired consistency. Glycereth 26 has a highermolecular weight than many other forms of Glycereth and a slowerevaporation rate, which results in longer lasting relief of dry skinsymptoms, including itching. Glycereth 26 can be obtained, for example,from Lipo Chemicals Inc., Paterson, N.J., as Liponic EG-1. However, in afurther embodiment, different forms of Glycereth can be used, includingGlycereth 1 through 30, in the amounts provided in the table above. Forexample, Glycereth 7 can be obtained, for example, from Lipo ChemicalsInc., Paterson, N.J., as Liponic EG-7. Also, as provided in the tableabove, the range of a PEG to Glycereth ratio can vary from a 5% PEG and95% Glycereth to a 95% PEG and 5% Glycereth. As the percentage of PEGincreases, the thicker the skin composition becomes. In one embodiment,50% of PEG is a maximum amount to prevent the skin composition frombecoming too hard. If too hard, the skin composition is difficult toapply. In a further embodiment, the Glycereth can be replaced with anyliquid polyethylene glycol, in the same amounts listed in the tableabove for Glycereth.

Once a ratio has been selected, the components, PEG 3350 and Glycereth7, are combined and heated to about 130 to 150 degrees until the PEG iscompletely dissolved. Once dissolved, the combined solution is stirredwhile cooling until a cream or ointment is formed. The skin compositioncan be stored in a plastic tube or bottle for providing to a patient inneed of relief. The patient squeezes the skin composition out of thetube or bottle onto his hands or fingers and rubs the cream into areasof dry skin. The skin composition should be applied as needed. This skincomposition is intended for use on rashes or itchy areas of skin thatare caused by dryness or other physical conditions, rather than forconditions that require medication, such as psoriasis or eczema.

The skin composition, described above in the preferred amounts, has beenused by about 20 individual human subjects for up to two years. Three ofthe individuals found the skin composition to be of marginal use, whilethree found the skin composition comparable with existing products. Theremaining individuals found the skin composition to be superior toexisting products by reducing a level of itching within minutes afterapplication. Further, the skin composition has the ability to relievedry skin symptoms, such as itching, throughout the day via a singleapplication, as long as the patient is not excessively sweating or goingswimming. When needed, the skin composition is easily removable from theskin and clothing.

While the invention has been particularly shown and described asreferenced to the embodiments thereof, those skilled in the art willunderstand that the foregoing and other changes in form and detail maybe made therein without departing from the spirit and scope of theinvention.

What is claimed is:
 1. An ophthalmic composition, consisting of: between10% and 25% weight of polyethylene glycol; between 15% and 30% weight ofglycereth; Carboxymethylcellulose Sodium; and water, wherein thecomposition is a viscoelastic gel that is formulated for ophthalmicadministration.
 2. The composition of claim 1, wherein the polyethylene2 glycol is polyethylene glycol
 3350. 3. The composition of claim 1,wherein the glycereth is glycereth
 26. 4. The composition of claim 1,wherein the composition is useful for at least one of increasing ocularcomfort and for providing relief of dry eye symptoms.
 5. The compositionof claim 1, wherein the composition is contained in at least one of aplastic tube, bottle, and eye drop dispenser.
 6. The composition ofclaim 1, wherein the composition is applied at least once a day to oneor more eyes.
 7. The composition of claim 6, wherein the composition isapplied to the inferior palperbral conjunctiva of the one or more eyes.8. The composition of claim 1, wherein the composition is applied via atleast one of an eye dropper and single use applicator.